chr2-27200477-CCT-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1_ModeratePM2PP5_Very_Strong
The NM_021095.4(SLC5A6):c.1865_1866del(p.Gln622ArgfsTer51) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,613,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000045 ( 0 hom. )
Consequence
SLC5A6
NM_021095.4 frameshift
NM_021095.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.197
Genes affected
SLC5A6 (HGNC:11041): (solute carrier family 5 member 6) Enables biotin transmembrane transporter activity and pantothenate transmembrane transporter activity. Involved in anion transmembrane transport and transport across blood-brain barrier. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0225 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
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Variant 2-27200477-CCT-C is Pathogenic according to our data. Variant chr2-27200477-CCT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1341577.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC5A6 | NM_021095.4 | c.1865_1866del | p.Gln622ArgfsTer51 | frameshift_variant | 17/17 | ENST00000310574.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC5A6 | ENST00000310574.8 | c.1865_1866del | p.Gln622ArgfsTer51 | frameshift_variant | 17/17 | 1 | NM_021095.4 | P1 | |
SLC5A6 | ENST00000408041.5 | c.1865_1866del | p.Gln622ArgfsTer? | frameshift_variant | 18/18 | 1 | P1 | ||
SLC5A6 | ENST00000461757.1 | n.1415_1416del | non_coding_transcript_exon_variant | 3/3 | 2 | ||||
SLC5A6 | ENST00000488743.6 | n.2551_2552del | non_coding_transcript_exon_variant | 16/17 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152128Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000439 AC: 11AN: 250398Hom.: 0 AF XY: 0.0000591 AC XY: 8AN XY: 135306
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GnomAD4 exome AF: 0.0000452 AC: 66AN: 1461734Hom.: 0 AF XY: 0.0000399 AC XY: 29AN XY: 727164
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Neurodegeneration, infantile-onset, biotin-responsive Pathogenic:3
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 02, 2022 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | Feb 01, 2021 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 08, 2023 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Oct 13, 2022 | Frameshift variant predicted to result in protein extension as the last 14 amino acids are replaced with 50 different amino acids, although loss-of-function variants have not been reported downstream of this position in the protein; This variant is associated with the following publications: (PMID: 31392107, 35217562) - |
Peripheral motor neuropathy, childhood-onset, biotin-responsive Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 08, 2023 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at